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| 024 | 7 | _ | |a 10.1038/s42255-025-01350-6 |2 doi |
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| 100 | 1 | _ | |a Coleman, Olivia I |0 0000-0002-4075-7820 |b 0 |
| 245 | _ | _ | |a ATF6 activation alters colonic lipid metabolism causing tumour-associated microbial adaptation. |
| 260 | _ | _ | |a [London] |c 2025 |b Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1756819028_26696 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a epub |
| 520 | _ | _ | |a Endoplasmic reticulum unfolded protein responses contribute to cancer development, with activating transcription factor 6 (ATF6) involved in microbiota-dependent tumorigenesis. Here we show the clinical relevance of ATF6 in individuals with early-onset and late colorectal cancer, and link ATF6 signalling to changes in lipid metabolism and intestinal microbiota. Transcriptional analysis in intestinal epithelial cells of ATF6 transgenic mice (nATF6IEC) identifies bacteria-specific changes in cellular metabolism enriched for fatty acid biosynthesis. Untargeted metabolomics and isotype labelling confirm ATF6-related enrichment of long-chain fatty acids in colonic tissue of humans, mice and organoids. FASN inhibition and microbiota transfer in germ-free nATF6IEC mice confirm the causal involvement of ATF6-induced lipid alterations in tumorigenesis. The selective expansion of tumour-relevant microbial taxa, including Desulfovibrio fairfieldensis, is mechanistically linked to long-chain fatty acid exposure using bioorthogonal non-canonical amino acid tagging, and growth analysis of Desulfovibrio isolates. We postulate chronic ATF6 signalling to select for tumour-promoting microbiota by altering lipid metabolism. |
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| 700 | 1 | _ | |a Sorbie, Adam |0 0000-0002-3330-4612 |b 1 |
| 700 | 1 | _ | |a Riva, Alessandra |0 0000-0002-5724-7616 |b 2 |
| 700 | 1 | _ | |a von Stern, Miriam |b 3 |
| 700 | 1 | _ | |a Kuhls, Stephanie |b 4 |
| 700 | 1 | _ | |a Selegato, Denise M |b 5 |
| 700 | 1 | _ | |a Siegert, Luisa |b 6 |
| 700 | 1 | _ | |a Keidel, Isabel |0 0009-0000-9806-1087 |b 7 |
| 700 | 1 | _ | |a Köhler, Nikolai |0 0000-0002-5103-883X |b 8 |
| 700 | 1 | _ | |a Wirbel, Jakob |0 0000-0002-4073-3562 |b 9 |
| 700 | 1 | _ | |a Kacprowski, Tim |0 0000-0002-5393-2413 |b 10 |
| 700 | 1 | _ | |a Dunkel, Andreas |b 11 |
| 700 | 1 | _ | |a Pauling, Josch K |b 12 |
| 700 | 1 | _ | |a Plagge, Johannes |b 13 |
| 700 | 1 | _ | |a Mediel-Cuadra, Diego |b 14 |
| 700 | 1 | _ | |a Wagner, Sophia J |b 15 |
| 700 | 1 | _ | |a Chadly, Ines |b 16 |
| 700 | 1 | _ | |a Bierwith, Sandra |b 17 |
| 700 | 1 | _ | |a Peng, Tingying |b 18 |
| 700 | 1 | _ | |a Metzler, Thomas |0 0000-0002-1620-5559 |b 19 |
| 700 | 1 | _ | |a Li, Xin-Feng |0 P:(DE-He78)0d56bfbd4cd4cf94f34df200f9d9f7c1 |b 20 |
| 700 | 1 | _ | |a Heikenwälder, Mathias |0 P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5 |b 21 |u dkfz |
| 700 | 1 | _ | |a Schafmayer, Clemens |b 22 |
| 700 | 1 | _ | |a Hinz, Sebastian |b 23 |
| 700 | 1 | _ | |a Röder, Christian |b 24 |
| 700 | 1 | _ | |a Röcken, Christoph |b 25 |
| 700 | 1 | _ | |a Zimmermann, Michael |0 0000-0002-5797-3589 |b 26 |
| 700 | 1 | _ | |a Rosenstiel, Philip |0 0000-0002-9692-8828 |b 27 |
| 700 | 1 | _ | |a Steiger, Katja |b 28 |
| 700 | 1 | _ | |a Jesinghaus, Moritz |b 29 |
| 700 | 1 | _ | |a Liebisch, Gerhard |0 0000-0003-4886-0811 |b 30 |
| 700 | 1 | _ | |a Ecker, Josef |0 0000-0003-4799-0788 |b 31 |
| 700 | 1 | _ | |a Schmidt, Christina |0 0000-0002-3867-0881 |b 32 |
| 700 | 1 | _ | |a Zeller, Georg |b 33 |
| 700 | 1 | _ | |a Janssen, Klaus-Peter |0 0000-0002-4707-7887 |b 34 |
| 700 | 1 | _ | |a Haller, Dirk |0 0000-0002-6977-4085 |b 35 |
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